Cardiac contractions (i.e. cardiac work) play a vital role in pumping blood from the heart to the organs, tissues, and cells in the human body, and are driven by the coronary artery providing blood (which contains oxygen, glucose, and nutrients mainly) to the myocardial cells. The myocardial cells then consume the oxygen and glucose in order to produce energy (which is ATP) for the heart to carry out further cardiac work. However, the following conditions may hamper blood supplies from reaching the heart properly: (1) when atherosclerosis occurs in the coronary artery and results in the narrowing of the blood vessel; (2) when the coronary artery becomes partially blocked (eg. by the formation of blood clots resulted from platelet aggregation); or (3) when the blood vessel becomes spasmodic and becomes restricted as a result. If the aforesaid conditions are accompanied by increased energy consumption in the human body (eg. during physical exercises), it can lead to insufficient blood supply to the cardiac muscles, which means there is a shortage of blood to the heart, and this in turn can result in angina. If the shortage of blood supply to the coronary artery persists and the cardiac muscles are left without blood for excessively long (from 15 seconds to 15 minutes), it would then lead to death of myocardial cells, which is medically described as myocardial infarction.
When a person experiences angina due to the shortage of blood supply to the cardiac muscles, the person is usually asked to take a rest because reducing cardiac work is the best treatment for angina. With reduced cardiac work, the heart requires less energy consequently, and this means the heart would require less of the substances (oxygen and glucose) needed for producing energy. Therefore, the blood supply from the coronary artery to the cardiac muscles could also be reduced, which relieves angina as a result. The medications used to reduce cardiac work in order to relieve angina can be divided into three types; first of which are nitrates, and second of which are β-blockers, whereas the third are calcium antagonists. The nitrates-based medications reduce cardiac work by: (1) widening the veins so as to keep the blood in the veins, which reduces the blood that circulates back to the heart, and the cardiac work is lowered as the heart does not need to pump as much blood consequently. The venous blood circulation is medically described as the preload, and nitrates are effective for lowering the preload. (2) widening the arteries to reduce the resistance within the blood vessels, such that there is not as much resistance for the heart to pump out the blood. Therefore, the required energy for the cardiac work is lessened as a result. The resistance within the arteries is medically described as the afterload, and nitrates are also effective for lowering the afterload. The β-blockers decrease the cardiac work by reducing the heartbeat, and the consumption of energy could be lowered along with the reduced cardiac work. The calcium antagonists mainly act on the arteries, which prevent calcium from flowing into the cells of the blood vessels, thereby widening the arteries and lowering the resistance within the blood vessels resulted from blood vessel contractions. Therefore, the cardiac work is reduced and the blood can be easily pumped into the organs and the tissues (ie. lowering the afterload).
Angina can be generally divided into three types, which are the stable angina, the unstable angina, and the Prinzmetal's angina. The stable angina is usually resulted from the narrowing of the coronary artery, and can be treated with the aforesaid three types of medication. The unstable angina is the result of fissure in the plaque generated from atherosclerosis of the coronary artery, which not only leads to varying degrees of vessel blockage due to different sizes of platelet aggregation, but also leads to vasospasms as well; both of which subsequently result in reduced blood flows to the coronary artery. This type of angina can also occur while the patient is resting, and the symptoms of which can last longer and be more damaging, and is a foretelling sign of acute myocardial infarction. This type of angina is treated by using the aforesaid three types of medication, in combination with the anti-platelet aggregation drugs, such as Aspirin. The Prinzmetal's angina is less common than the other two types, and is the result of a spasmodic coronary artery. It can be treated by using the calcium antagonists, or by directly widening the coronary artery from using nitrates.
According to past research literature, green tea possesses many chemical components and medicinal properties. Among the chemical components of green tea, tea polyphenols is the term used to describe all polyphenol substances found in tea leaves, which include flavanols, anthocyanins, flavonoids, flavonols, and phenolic acids. The flavanols are the most abundant compounds among the tea polyphenols, they are also called the catechins. In green tea, the main compounds that make up the catechins are catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), epigallocatechin gallate (EGCG), gallocatechin-3-gallate (GCG), gallocatechin (GC), and catechin-3-gallate (CG).
The catechins occupy approximately 70% of the tea polyphenols in total, and are particularly considered as the main health-promoting component therein. A large number of research literature have shown the medicinal properties thereof, such as: anti-oxidation, anti-inflammation, anti-viral, anti-cancer, anti-atherosclerosis properties, and the ability to reduce weight in test subjects. The relationship between tea and cardiovascular diseases has been extensively studied in the past, which was carried out by using tens of thousands of healthy people from Japan, the Netherlands, and the U.S. as the test subjects, and lasted for six to seven years. The studies had found that drinking tea is closely correlated to lowering the occurrence and risks of cardiovascular and cerebral vessel diseases, and is therefore beneficial to the health of the tea drinkers.
The cardiovascular and cerebral vessel diseases have always been the top three causes of death among the ten most common fatal diseases, and there are approximately 1 million people suffering from myocardial infarction (MI) in the U.S. alone every year.
Myocardial infarction is generally treated by employing thrombolysis, angioplasty, or coronary bypass graft surgery. However, the focus of the present invention is on providing a medication that could delay the death of cardiac muscles when the myocardial cells are dying because of insufficient blood (which is irreversible and called myocardial infarction medically) even though the blood is continuously supplied, or salvage the heart while the cardiac muscles suffer from reversible damage. From the viewpoint of biochemical changes, the death of cardiac muscles is resulted from insufficient blood supply thereto, which in turn leads to insufficient supplies of oxygen and glucose thereto, consequently preventing enough energy (ATP) from being produced in the cardiac muscles and damaging the myocardial cells. Subsequently, the energy insufficiency causes the sodium pumps in the ATP-dependent cell membrane to stop functioning properly, which in turn causes the extracellular sodium, calcium, and water molecules to rush into the cells and make the cells swell up, although the phenomenon is still reversible at this stage. If blood supply is resumed now, the cells could be returned to normal. But if the blood insufficiency continues, the intracellular lysosomes would become lysed, which releases many types of degradation enzymes (such as the degradation enzymes of proteins, lipids, and nucleic acids, etc.) into the intracellular space, along with many kinds of biochemical substances, and the cell membrane are damaged as a result. An important factor that causes the aforesaid catastrophic process is ATP insufficiency, which leads to elevated calcium concentration intracellularly. This is critical because an elevation in calcium concentration actually activates the released enzymes, and further damages the affected cells. Biochemically speaking, the death of cardiac muscles goes through three stages: (1) a shortage of blood leads to ATP insufficiency; (2) the intracellular calcium concentration is elevated subsequently; (3) the lysosomes are released as a result. The damage sustained from up to the second biochemical stage is still reversible. Even though the cells appear to be swelling, the myocardial cells can still be salvaged by supplying oxygen/glucose at this stage. However, the damage sustained from the third biochemical stage is irreversible, and would lead to inevitable death of the cardiac muscles. In the U.S. patent US 2006/0116333 A1, a pharmaceutical composition comprising tea polyphenols for protecting and preserving organs, tissues, or cells has been disclosed, which is applied in a person undergoing an organ transplant operation, so as to protect the person from suffering from organ damage. The damage described in this patent differs from the aforementioned damage caused by partial blood insufficiency in that the heart is still carrying out cardiac work (cardiac contrations) under limited ATP. But when a person undergoes an organ transplant, the heart would have stopped working when it is removed from a human body. Once the heart is transplanted into another human body, it then gives rise to ischemia-reperfusion damage consequently. The ischemia-reperfusion damage occurs because when blood is re-supplied, the oxygen in the blood leads to the production of a new type of enzyme called xanthine oxidase in the cardiac muscles, which is subsequently transformed into harmful free radicals (such as —O2−, H2O2, and —OH), and damages the cell membrane by peroxidation of lipids therein. In other words, the damage of an organ during an organ transplant is resulted from the generation of free radicals when blood is re-supplied, and the damage can be effectively prevented by providing anti-oxidative substances (which mops up the free radicals). The anti-oxidative substances used in the aforesaid patent are the commonly known tea polyphenols. According to the openly published data herein, the cardiac muscles show signs of swelling when the heart is removed from a human body. This means that when the heart is being transplanted, the heart only suffers from reversible damage and not the death of cardiac muscles. Therefore, cardiac damage caused by blood insufficiency (angina) and ischemia-reperfusion damage (organ transplant) is different in nature.